The present invention relates in general to fluorinated polymers. More specifically, the present invention relates to fluorinated networks for anti-fouling surfaces.
The accumulation of microorganisms on wetted surfaces, or biofouling, is a common challenge for materials in a broad range of applications, such as medical devices, marine instruments, food processing, and even domestic drains. Generally, bacteria initiate biofouling by forming of biofilms, which are highly ordered adherent colonies, frequently within a self-produced matrix of extracellular polymeric substance. Biofilms can accumulate, for example, on surfaces of medical devices, including implantable medical devices, as well as surfaces in hospital or medical settings.
Biofilms potentially release harmful toxins, and microorganisms easily spread once biofilms are formed, which can lead to malfunction of implantable devices. Once a biofilm is formed on an implantable medical device, extreme measures, such as removal of the infected implanted device from the patient's body are often the only viable management options. Although disinfection techniques and prophylactic antibiotic treatment are used to prevent colonization during procedures, such practice is not always effective in preventing perioperative bacterial colonization.
Antibiotic treatments to eliminate colonization and infection associated with implantable substances and devices can be limited in their ability to eradicate bacteria and fungi involved in biofilm formation processes. For example, the concentration of antibiotics deep inside the biofilm can be too low to be effective, which is in part due to limited diffusion. Generally, antibiotics also may be unable to eliminate all pathogen cells, which are usually accomplished by the immune system that may not function optimally in the presence of implantable devices. Furthermore, microorganisms possess the ability to persist, i.e., to become metabolically inactive and thus relatively resistant to antibiotics. Antibiotic resistance thus makes treating device-associated infections even more challenging. In fact, antibiotic resistance is frequently encountered with microorganisms that cause device-associated infections (e.g., Enterococci and Staphylococci).
Consequently, considerable efforts were dedicated in recent years to developing antibacterial surfaces, in particular, in developing antifouling surfaces that prevent the adhesion of microorganisms. Current technologies, however, can suffer from poor long-term antibacterial performance and stability, the undesirable development of bacterial resistance, or limited scalability to an industrial setting.
Accordingly, there is a need to prevent surfaces of medical devices from forming biofilms and fouling. Forming polymeric coatings on surfaces of medical devices is one option to prevent biofouling.
Polythioaminals are a potential polymer that could be useful for forming such a coating. Polythioaminal polymers have potential applications in numerous arenas, for example, in facile preparation of therapeutic/drug conjugates, self-healing materials, and degradable hydrogels. Scheme 1 below depicts a reaction for synthesizing polythioaminals using hexahydrotriazine (HT). A dithiol (1) reacts with HT (2), releasing a substituted primary amine (3) to form the substituted polythioaminal (4).

HTs, as shown in Scheme 1, and their thermosetting polymer analogues, PHTs, have attracted recent attention in the materials space because they exhibit a number of attractive properties, such as healability, recyclability, and even as detectors for heavy metals. HTs also demonstrate unique reactivity towards sulfur containing compounds. Hydrogen sulfide, for instance, readily reacts with HTs at room temperature to form dithioazine, where the six-member HT ring undergoes replacement of two nitrogen atoms with sulfur. Organic thiols will also react with HTs to produce thioaminals, as shown in Scheme 1, a transformation that has been exploited to generate linear step-growth polythioaminals.
However, current synthetic routes, for example as shown in Scheme 1, for forming polythioaminals have some challenges that have made them sub-optimal for such applications. A limiting factor in the polymerization shown in Scheme 1 above is the identity of the substituent of the HT (2) (“X”). In particular, as the size of “X” increases, the molecular weight of the polymer decreases. Therefore, high molecular weight polymers are only generated with short aliphatic HT substituents, which restrict the chemical diversity of the resulting polymers.
The relationship between the size of the HT (2) substituents, “X,” and the product polythioaminal (4) molecular weight is the result of the substituted primary amine (3) generated after the reaction of the dithiol (1) with the HT (2). The formation of this amine (3) influences the reaction equilibrium, preventing further reaction of thiols (1) with HTs (2) and necessitating subsequent removal (in vacuo) to access high molecular weight polythioaminals (4). Therefore, as the mass of the substituent (“X”) increases, the volatility of the liberated substituted primary amine (3) is reduced, thereby making the polymerization increasingly difficult to drive to high molecular weights.
Therefore, alternative chemistries that can provide access to polythioaminals that are not restricted by the volatility of a side product are needed. Such chemistries can provide access to more chemically diverse polymers, which can allow polythioaminal polymers to be used as coatings on surfaces, such as medical devices.